The overall goal of this proposal is to identify the regulatory role of the aryl hydrocarbon receptor (AhR) interacting with NF-?B signaling in controlling function and differentiation of dendritic cells (DC). Alteration of cellular communication of DC with T cells can lead to immunological disorders like autoimmune diseases, allergy and immunodeficiency. Especially interaction of the AhR with NF-?B RelB mediated pathways critical for appropriate immune responses will be the focus of this study. DCs are key regulator of immunity or tolerance, and the NF-?B members RelA and RelB are critical for the development, differentiation and function of DC. Therefore, the AhR may interact with NF-?B Rel proteins to regulate the function of DCs, which affects T cell differentiation in particular pathological conditions mediated by activation of NF-?B and AhR. This study can provide a definite link and mechanism between the exposure to persistent organic pollutants like dioxin and dioxin-like compounds activating the AhR and the development of diseases based on their immunotoxic effects. This will allow for more clearly defined endpoints to assess the effects of AhR activating compounds and may also provide opportunities to develop new substances that can then be used to manipulate the immune system and allow for effective preventative measures to be implemented.

Public Health Relevance

The present study focuses on a novel concept of the function of aryl hydrocarbon receptor (AhR) in cross-talk with NF-?B signaling pathways important for the understanding how the transcriptional potential and activity of the AhR is implemented in the differentiation and function of dendritic cells in the immune system. The current study is critical in understanding the potential biological function of the AhR in the immune system and its role in immunological disorders like allergy or autoimmune disease. This work will help to understand the mechanism how environmental toxicants like dioxin or dioxin-like compounds, which activate the AhR, affect critical functions of the immune system and human health.